a) Field of the Invention
This invention relates to novel 1-cyclopropyl-3 substituted-5-R3-6-fluoro-8-R4-7-(2-R1-6-R2-4-pyridyl)-1,4-dihydro-quinoli n-4-ones and their pharmaceutical compositions, and a method of treating malignancy with these compounds.
b) Information Disclosure Statement
Gilligan et al., U.S. Pat. No. 4,623,650 issued 18 Nov. 1986, discloses 1-substituted 6,8-difluoro-7-aryl-1,4-dihydroquinol-4-one 3-carboxylic acids stated to have antibacterial activity.
Schriewer et al., U.S. Pat. No. 4,705,788 issued 10 Nov. 1987, discloses novel antibacterially active 7-amino-1-(substituted cyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids of the formula ##STR2## in which
X.sub.1 and X.sub.2 can be identical or different and represent hydrogen or halogen;
R.sub.1, R.sub.2 and R.sub.3 represent hydrogen, methyl, chlorine or fluorine, the radicals R.sub.1 -R.sub.3 never all being identical; and
R.sub.4 and R.sub.5, together with the nitrogen atom to which they are bonded, form a 5-membered or 6-membered heterocyclic ring which may be substituted.
Mosuzawa et al., U.S. Pat. No. 4,791,118, issued 13 Dec. 1988, discloses quinolonecarboxylic acid derivatives of the following formula ##STR3## wherein
R is hydrogen atom or lower alkyl group;
Alk is lower alkylene group; and
X is hydrogen atom or halogen atom; the hydrates and pharmaceutically acceptable salts thereof are stated to be useful as antibacterial agents.
Peterson et al., U.S. Pat. No. 4,820,716, issued 11 Apr. 1989 discloses 7-(1-pyrrolidinyl)-3-quinolonecarboxylic acid derivatives of the formula ##STR4## in which
A is CH, CCl, CF or N;
R.sub.1 is hydroxyl, hydroxymethyl or mercapto; and
R.sub.2 is hydrogen, alkyl, having 1 to 4 carbon atoms or (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl; with the proviso that, when R1 is hydroxy, A is not CF or N, or pharmaceutically acceptable hydrates or salts thereof are stated to be useful as antibacterials and animal feed utilization promoters.
Schriewer et al., U.S. Pat. No. 4,908,366, issued 13 Mar. 1990, discloses compounds of the formula ##STR5## in which
Y represents a carboxyl group, a nitrile group, an ester group --COOR.sub.1 or an acid amide group --CONR.sub.2 R.sub.3 ;
X.sub.1 represents hydrogen, nitro, alkyl or halogen;
X.sub.4 can be hydrogen or halogen, or alkyl;
R.sub.4 and R.sub.5, together with the nitrogen atom to which they are bonded form a 5- or 6-membered heterocyclic ring which can additionally contain the atoms or groups --O--, --S--, --SO--, --SO.sub.2 -- ##STR6## as ring members of the group ##STR7## can also represent a ring system of the structure ##STR8## which can optionally be substituted on the ring carbons by methyl and pharmaceutically usable hydrates, salts or esters thereof.
These compounds are stated to have a high antibacterial activity and therefore to be suitable as active compounds for human and veterinary medicine.
Bridges et al., U.S. Pat. No. 4,933,335, issued 12 Jun. 1990, discloses a series of quinolone carboxylic acids which are stated to have use as antibacterial agents.
Groche et al., U.S. Pat. No. 4,952,695, issued 28 Aug. 1990, discloses 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and ester as pharmaceutical intermediate.
Wentland, U.S. Pat. No. 4,959,363, issued 25 Sep. 1990, discloses compounds of the formula ##STR9## where
R is hydrogen, hydroxy, amino or lower-alkyl;
R.sub.1 is lower-alkyl, lower-alkenyl, cycloalkyl, pyridinyl, phenyl or substituted phenyl
R.sub.2 is hydrogen, amino or hydroxy;
R.sub.6 is hydrogen or fluoro; and
R.sub.7 is phenyl, pyridinyl or selected other heterocycles; The compounds are stated to have antiviral activity against herpes virus.
Lesher et al., U.S. Pat. No. 5,075,319, dated Dec. 24, 1991, discloses fluorinated 1-cyclopropyl-7-(substituted-pyridinyl)-l,4-dihydro-4-oxo-3-quinolinecarbo xylic acids of the formula ##STR10## wherein
R is hydrogen;
R' and R" are hydrogen or fluoro, or other groups; and
Z is 3- or 4-pyridinyl substituted by alkyl groups or substituted alkyl groups. The compounds are stated to be superior antibacterial agents.